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Biomedical subjects

J Braun

Publications and source records attributed to J Braun.

At least 433 records · Page 24Linked to original sources

In situ lacZ retrovirus-marked lymphocytes define a B cell microenvironment in the lymph node medulla.

A recombinant nonreplicating retroviral vector bearing the Escherichia coli lacZ indicator gene was used to mark a population of B cells in situ in murine lymphoid tissue. The retrovirus was surgically injected into popliteal lymph nodes during the primary immune response to DNP-CGG when B cell proliferation in the germinal centers was maximal. LacZ+ cells were initially detected in the perivascular medullary interstitium, where they expanded and persisted up to 2 weeks following retrovirus injection. Migrant lacZ+ B cells were detected in the spleen 3-18 weeks following immunization and resided in the red pulp or marginal zones. Two-color flow cytometric analysis using a fluorogenic substrate for beta-galactosidase revealed that lacZ+ cells bear kappa light chains and that at least 50% of these cells bound the hapten, DNP. Based on their location, life span, migratory capacity, antigenic specificity, and surface immunoglobulin density, lacZ+ cells define a distinct nonfollicular B cell population associated with other late developmental stages of B lymphocytes, including memory and plasma cells.

Animals↗

[Transposition of the gluteus maximus muscle for sphincter replacement in anal incontinence].

The replacement of the external anal sphincter by gluteus muscle in fecal incontinence is described in 4 cases. All patients, three children and one adult, had been operated on previously because of different types of anal atresia and suffered from fecal incontinence grade IV. They all showed a congenital defect of the somatic sphincter. The absent external and sphincter muscle was repaired by transposing innervated and vascularized gluteus muscle. In all cases active anal continence was achieved proven by clinical and electromanometric measures. The results, compared to other techniques, are discussed.

Adult↗

Obstructive colorectal carcinoma. Principles and technique in 134 cases.

In order to define the influence of intestinal obstruction on therapy and prognosis of colorectal carcinoma, we analyzed retrospectively the records of 1756 patients with this type of malignancy (1966-1990). The incidence of obstruction was 8% among our patients (n = 134), 3% of which suffered perforation (n = 4). Operative mortality was 30% as compared to 7% after elective surgery. Curative resections could be performed in only 34%, while this was possible in 75% of non-obstructive cancers. 5-year survival dropped from 51% to 23% in cases with obstruction. The choice of operative procedure depends mostly on tumor localization. Tumor obstructions of the right colon benefit from primary resection, while this advantage could not be demonstrated for left-sided lesions. Still, we consider it in any case desirable to remove the malignancy during the initial operation. In recent years, the number of one-stage procedures has increased dramatically, while mortality was reduced.

Colorectal Neoplasms↗

[Rectal cancer--results of continence-preserving resections].

In a series of 586 patients with rectal carcinoma who underwent potentially curative resection between January 1977 and December 1990 postoperative complications, incidence of local recurrence and disease free survival are investigated. Of the 401 patients undergoing low anterior resection (LAR) and 89 patients with coloanal anastomosis (CAA) 389 anastomoses were fashioned with staples. The hospital mortality rate was 4.6%. Clinical anastomotic leakage occurred in 5.5% (handsewn 10.3% stapled 4.3% (p less than 0.05), anastomotic strictures in 7.5% and 2.4% (p less than 0.05). 20% of patients undergoing restaurative resection (RR) (handsewn 23%, stapled 20%) developed local recurrences compared with 21% for the group with abdominoperineal resection (APR). The corrected 5-year survival rate was 63% for RR respectively 55% for APR (p greater than 0.05). After CAA, incidence of local recurrence and survival rate for patients with carcinoma of the lower rectum was 11% respectively 63%. It is concluded that innovative advances like the development of circular stapling devices and the adoption of a more aggressive sphincter-saving policy like CAA cause not an increased risk of recurrent diseases and no decrease of the 5-year survival rate.

Adult↗

In vivo retroviral marking of antigen-specific B lymphocytes.

A major obstacle in the study of B lymphocyte development subsequent to immunization has been the paucity of distinctive phenotypic markers which might permit the separation and scrutiny of a mature antigen-experienced or memory cell population. To address this issue, we have introduced a recombinant non-replicating retrovirus into antigen-reactive lymph nodes in vivo using the expression of a reporter gene to monitor the trafficking, phenotype and persistence of retrovirus-marked B cells. Marked cells are first observed in the medullary cords where they proliferate for approximately 10 days prior to migration to the spleen. Up to half of the marked cells bear antigen-specific immunoglobulin receptors, but otherwise phenotypically resemble conventional B cells. The abundance and persistence of the marked cells suggest an association with the memory compartment. These experiments demonstrate a feasible approach for the identification and lineage analysis of antigen-responsive B cells, and suggest that the lymph node medulla supports a transient phase of post-antigenic B cell development associated with a long-lived antigen-specific B cell subset.

Animals↗

[High-dose-rate brachytherapy of prostatic carcinoma with iridium 192].

In the therapy of localized prostatic cancer the radical prostatectomy shows good results within a five-year interval with no evidence of disease in nearly 90%. An important alternative is the radiotherapy by external beam or interstitial technique with iodine, gold or iridium. We use the high dose rate technique with Ir-192. In this technique five to seven hollow needles are placed in the prostate from perineal punctures under transrectal sonographic control. The three-dimensional brachytherapy planning is done according the actual needle position. A computer program calculates the radiation dose and distribution for each needle by adjustment of time and stops of the Ir-implants. The Ir-192 is temporary loaded twice with 9 Gy supplemented with external beam radiation (18 x 2 Gy). Since 1985 29 patients with localized tumor (T1-T3, N0, M0) have been irradiated. 21/29 had a pelvic lymphadenectomy before. In 85% of the patients were seen no side effects. Only one patient had a serious complication through a recto-vesical fistula. Out of the 21 followed-up patients 16 were in full remission, three had an androgen deprivation because of progression. A local tumor control could be demonstrated by cytology in 70% of the patients. This rational technique seems to be an alternative for patients not eligible for a radical prostatectomy.

Aged↗

A VH clonal deficit in human immunodeficiency virus-positive individuals reflects a B-cell maturational arrest.

A major feature of human immunodeficiency virus (HIV) infection is disordered B-cell function, which paradoxically includes both pathologic overactivity (elevated serum antibodies, lymphadenopathy, and increased risk for lymphoma) and underactivity (impaired antibody immunity, particularly to bacterial polysaccharide antigens). B-cell immune dysfunction contributes significantly to HIV-related morbidity and also represents an obstacle to eventual definitive treatment by anti-HIV immunization. Our laboratory has recently identified in normal B-cell populations certain VH gene subfamilies with a developmentally regulated pattern of utilization. In particular, B cells bearing rearranged VH3L were rare in the germinal center but uniformly abundant in the blood and lymphoid mantle zone. We used this index gene subfamily as a clonal criterion for the pattern of B-cell development in lymphocytes of HIV-positive individuals. In a series of 19 HIV-positive subjects, a striking deficit of VH3L B cells was observed; in contrast, none of the 16 normal subjects showed this abnormality. Other VH subfamilies (VH1N, VH4/6, and VH5N) were unaffected in the HIV-positive patients. This VH3L clonal deficit and other recent phenotype and histopathologic findings suggest that the general B-cell dysfunction in HIV is due to a discreet maturational arrest at the germinal center stage.

B-Lymphocytes↗

Glutaric aciduria type I. Brain CT features and a diagnostic pitfall.

Serial CT findings in an infant with glutaric aciduria type I (GA-I) are reported. The major CT features were dilatation of the insular cisterns, regression of the temporal lobes, with "bat wings" dilatation of the Sylvian fissures and hypodensity of the lenticular nuclei. CT changes preceded the onset of symptoms by 3 months. An improvement in the temporal lobe atrophy was seen after a period of treatment, coinciding with marked clinical improvement. A peculiar feature was the presence of external hydrocephalus, which diverted the attention from manifestations of the primary disease and thus constituted a diagnostic pitfall. The delineation and recognition of the characteristic radiologic manifestations of GA-I are essential for allowing an adequate radiologist/clinician interaction in diagnosing this inborn error of metabolism.

Amino Acid Metabolism, Inborn Errors↗

The temporal bone in the Johanson-Blizzard syndrome. A CT study.

The findings of thin-section high-resolution CT of the temporal bone in two children with Johanson-Blizzard syndrome are reported. In both cases an anomaly of the inner ear was found, consisting of bilateral cystic dilatation of the cochlea and the vestibulum. The possible etiologic basis for the hearing loss in this syndrome is discussed and the literature is reviewed.

Child↗

Anal sphincter function after intersphincteric resection and stapled ileal pouch-anal anastomosis.

This study was done to determine the effect of the direct ileal pouch-anal anastomosis upon pressure and sensory components of the anal canal and ileal pouch. These findings were related to postoperative continence. Thirty-three patients with ileal pouch-anal anastomosis (25 continent, eight with episodic minor incontinence) were studied 3 +/- 0.3 and 25 +/- 5 months after ileostomy takedown. The maximum resting pressure in the anal canal was significantly lower in patients with an imperfect result (35 +/- 5 mm Hg) than in continent patients (44 +/- 5 mm Hg) (P less than 0.05). Postoperatively the maximum squeeze anal pressure was slightly greater in continent than in incontinent patients (99 +/- 8 mm Hg vs. 87 +/- 7 mm Hg) (P greater than 0.05). The postoperative recto-(ileo-)anal inhibitory reflex was present in 27 percent. The linear correlation between strength of rectal (ileal) distension and depth resp. duration of internal sphincter relaxation as preoperatively observed disappeared postoperatively in every group of patients. Simultaneous measurements of pouch and anal pressure in patients with imperfect results revealed a reduced positive pouch anal pressure gradient compared to the continent group. This low pouch-anal pressure gradient is thought to be responsible for the increased incidence of soiling in some of our patients.

Adenomatous Polyposis Coli↗

Visceral leishmaniasis mimicking a flare of systemic lupus erythematosus.

Fever in systemic lupus erythematosus (SLE) may be caused by exacerbation of the disease itself or by infection. We report on a patient with a long standing history of SLE that was complicated by fever and pancytopenia with no splenomegaly. SLE disease activity was suspected because of an elevated DNA-antibody titer. The early positive response to corticoid therapy may have masked the underlying infection. Visceral leishmaniasis was diagnosed by a repeated bone marrow biopsy and serological testing.

Animals↗

Human immunodeficiency resulting from a maturational arrest of germinal center B cells.

Common variable immunodeficiency (CVI) is an acquired human disorder involving a striking and heterogeneous maturational defect of B lymphocytes. In this study, we used a recently developed VH gene utilization assay to analyze the abundance of developmentally restricted and unrestricted V genes in blood B cells from nine CVI patients. Unrestricted clones (bearing rearranged VH5, VH4, or VH6 genes) were present in normal abundance in this group of CVI patients. However, clones bearing VH3L, a subgroup of the VH3 family normally abundant in blood B cells but absent in B cells at the germinal center stage, were deficient in seven of nine CVI patients. Based on these findings and a reconsideration of previously reported B cell features in CVI, we propose that the disorder represents in most cases a maturational arrest of B cells at the germinal center stage.

Antigens, Differentiation, B-Lymphocyte↗

Texture-based tasks are little affected by second tasks requiring peripheral or central attentive fixation.

Experiments are described in which observers attempted to perform concurrently two separate visual tasks. Two types of tasks were used: the identification of a T-shaped or L-shaped letter target, and the detection or localization of a texture element of unique orientation (texture target) within a dense texture. Combining these tasks to form various task pairs, performance as a function of stimulus onset asynchrony (SOA) was established separately for each task in a pair. In addition, performance was measured when each task was carried out by itself. When paired, two identification tasks (T or L) on (two) letter targets required a significantly larger SOA than either identification task by itself. This outcome suggests the involvement of serial performance and competition for a limited resource, confirming that letter identification requires attentive fixation. However, when the identification of a central letter target was paired with the localization (upper or lower hemifield) of an eccentric texture target, performance in the pair was comparable to performance of each task by itself. This suggests parallel performance and a lack of conflict over resources. The outcome was similar when the identification of an eccentric letter target was paired with the detection (present or absent) of an eccentric texture target. These results are consistent with the possibility that localization and detection of a textural singularity do not require attentive fixation.

Attention↗

Independent rearrangement of Ig lambda genes in tissue culture-derived murine B cell lines.

Rearrangement of the lambda light chain locus is considered a late event in pre-B cell differentiation which occurs after successful heavy chain and unsuccessful kappa light chain rearrangement. However, this view has recently been challenged by the observation of apparently independent lambda rearrangement in certain B cell lines and Ig transgenic populations. In this study we have examined the pattern of Ig rearrangements and expression in several tissue culture-derived murine B cell lines. One pre-B cell line (BDL-1) displayed germline heavy and kappa light chain genes despite the presence of a productive lambda 1 light chain rearrangement. Two other cell lines (DAC-2, BDL-2) had multiple lambda rearrangements despite the presence of productive kappa chain rearrangements. These cell lines provide new precedents for rearrangement of the lambda locus independent of the kappa locus. Their phenotype suggests that accessibility at the different Ig loci may be controlled by a non-sequential mechanism.

Animals↗

Evaluation of the acrosome reaction using monoclonal antibodies against different acrosomal antigens--comparison with the triple stain technique.

The acrosome reaction of human sperm was evaluated in vitro with the aid of there monoclonal antibodies TüS-1, TüS-19 and TüS-20, which react with antigens in the anterior part of the acrosome. Data were compared with results obtained using the triple stain technique. Seminal smears were performed prior to, and following incubation for 5 and 24 h in Hams-F10 containing 3% human serum albumin. Using the triple stain technique, 15.2 +/- 7.1% of sperm exhibited acrosome activation after 5 h and 16.8 +/- 8.4% after incubation for 24 h. The corresponding values obtained using antibody TüS-1 were 12.9 +/- 5.8 and 13.2 +/- 2.2%, with TüS-19 10.1 +/- 3.8 and 10.8 +/- 1.4% and with TüS-20, 9.0 +/- 3.4 and 10.4 +/- 2.9%. When the same sperm smears were stained firstly with rose Bengal, and secondly with TüS-1 both methods stained the same cells and the same region of the cells, thus indicating that both methods stain the same substrate. Staining of the acrosome with monoclonal antibodies gives clearer results than the triple stain technique, and could be used in preference in future studies dealing with diagnosis of the acrosome reaction in vitro.

Acrosome↗

Limited B cell repertoire in severe combined immunodeficient mice engrafted with peripheral blood mononuclear cells derived from immunodeficient or normal humans.

The ability to engraft human PBMC or fetal tissue immune cells in the severe combined immunodeficient (SCID) mouse has created a need for characterization of these systems and their application to disease models. We demonstrate that SCID mice reconstituted with PBMC support the growth and differentiation of a restricted set of B cells. Human IgG levels of 1-2 mg/ml (10-20% of normal human serum levels) were routinely achieved in spite of a serum half life of only 12 d. Ig levels peaked around 50 d and Ig production was maintained for greater than 100 d. The Ig was greater than 85% IgG though some IgM, IgA, IgD, and even IgE could be detected. However, the human IgG produced in hu-PBL-SCID mice was pauci-clonal when analyzed by isoelectric focusing and by kappa/lambda light chain usage. Using a new polymerase chain reaction based analysis capable of monitoring individual VH family utilization, we found that the engrafted B cells showed skewed and restricted human VH subfamily utilization. These parameters were markedly variable among hu-PBL-SCID mice reconstituted from the same donor cell population at both early (21-50 d) and late stages (greater than 100 d). Hu-PBL/CVI-SCID mice constructed with cells from patients with common variable immunodeficiency with an in vitro block in terminal B cell differentiation produced human Ig responses that were quantitatively the same as those produced by hu-PBL-SCID mice from normal donors. The hu-PBL-SCID system using PBMC appears to lead to growth and Ig production by a small number of B cells and results in a restricted B cell repertoire.

Animals↗

[Non-Hodgkin's lymphomas of the stomach. Therapy from the surgical viewpoint].

About 2-5% of all gastric tumours are Non-Hodgkin Lymphomas (NHL). In the last years we treated 15 patients with NHL of the stomach. Six of these patients were classified to group IE according to Ann Arbor classification, four to group II (three II 1 E and one II 2 E). In group III E were two patients (one III S and one III E) and one patient was classified to group IV. Ten patients displayed low grade and five high grade malignancies with respect to the Kiel classification. We performed in group I three gastrectomies and three BI resections. In four patients of group II two gastrectomies and two BI resections were carried out and in group III two BI resection. Our treatment policy consisted of operation and radiation in IE, to operation and chemotherapy in high grade lymphomas of group II, and operation plus radiation in low grade malignancies of group II. In group III we treated radiation, chemotherapy and operation and in group IV radiation and chemotherapy. In group I five patients survived, in group II two out of four and in group III one of two. The patient of group IV died within two years after diagnosis.

Adult↗